OBJECTIVESThe aim of this study was to investigate the relevance of inflammation in the pathogenesis of abdominal aortic aneurysm (AAA) in vivo with two novel positron emission tomography (PET) tracers: [(11)C]-PK11195 which targets the translocator protein (18 kDa) expressed on macrophages and [(11)C]-d-deprenyl with a yet unknown target receptor expressed in chronic inflammation.DESIGNProspective clinical study.MATERIALS/METHODSFive patients were examined with [(11)C]-PK11195-positron emission tomography/computed tomography (PET/CT) and 10 with [(11)C]-d-deprenyl-PET/CT. Nine large AAAs (54-66 mm) scheduled for repair and six small AAA (35-44 mm). All 15 patients were male and the AAAs were all asymptomatic. Regional activity was measured as standardised uptake values (SUVs) and retention index was calculated. Biopsies were taken from the aneurysm wall for histological examinations, in the nine patients operated on.RESULTSNo aortic uptake was recorded on the visual inspection, neither with [(11)C]-PK11195 nor with [(11)C]-d-deprenyl. For [(11)C]-PK11195 the median SUV of the AAA wall was 0.9 (range 0.8-1.0) and for [(11)C]-d-deprenyl, 0.7 (range 0.4-1.2). No increased uptake was seen in the aneurysmal infrarenal aorta compared with the non-aneurysmal suprarenal aorta. Histological examination of the aneurysm wall showed high inflammatory cell infiltration with lymphocytes and macrophages.CONCLUSIONSThe chronic inflammation observed in the vessel wall was not detectable with [(11)C]-PK11195 and [(11)C]-d-deprenyl. In order to study the relevance of the inflammation in the pathogenesis of AAA in vivo other PET tracers need to be investigated.

01 Jul 1995·Journal of nuclear medicine : official publication, Society of Nuclear Medicine

Selective reduction of radiotracer trapping by deuterium substitution: comparison of carbon-11-L-deprenyl and carbon-11-deprenyl-D2 for MAO B mapping.

Article

Author: Xie, S ; Logan, J ; Wang, G J ; Schlyer, D J ; Volkow, N D ; MacGregor, R R ; Fowler, J S ; Alexoff, D L ; Patlak, C ; Pappas, N

Recent human PET studies with the monoamine oxidase B (MAO B) tracer [11C]L-deprenyl show that the rapid rate of radiotracer trapping relative to transport reduces the sensitivity of the tracer in regions of high MAO B concentration. This study investigates the use of deuterium substituted L-deprenyl ([11C]L-deprenyl-D2) to reduce the rate of trapping in tissue and to improve sensitivity.METHODSFive normal subjects (43-64 yr) were studied with [11C]L-deprenyl and [11C]L-deprenyl-D2 on the same day. Time-activity data from different brain regions and the arterial plasma were analyzed using a three-compartment model as well as graphical analysis for irreversible systems.RESULTSFor both tracers, maximum radioactivity accumulation occurred at about 5 min. For [11C]L-deprenyl, 11C concentration peaked at 5 min and remained constant throughout the study. With [11C]L-deprenyl-D2, peak 11C concentration also occurred at about 5 min but was followed by an initial washout. Carbon-11 concentration generally plateaued from 30 to 60 min. The plateau for [11C]L-deprenyl was higher than the plateau for [11C]L-deprenyl-D2. Data analysis by a three-compartment model and by graphical analysis showed that deuterium substitution: (a) does not affect plasma to tissue transport (K1); (b) reduces the rate of trapping of 11C in all brain regions; (c) facilitates the separation of model terms related to radiotracer delivery from radiotracer trapping in tissue; and (d) improves tracer sensitivity.CONCLUSIONThis study demonstrates that deuterium substitution causes a significant reduction in the rate of trapping of labeled deprenyl, providing a direct link between radiotracer uptake and MAO B in the human brain and enhancing tracer sensitivity to changes in MAO B concentration.

Acta Pharmacologica Sinica

Preclinical characterization of [18F]D2-LW223: an improved metabolically stable PET tracer for imaging the translocator protein 18 kDa (TSPO) in neuroinflammatory rodent models and non-human primates

Article

Author: Zeng, Chun-yuan ; Jiang, Yuan-fang ; Li, Yin-Long ; Wang, Lu ; Hou, Lu ; Liang, Steven H. ; Bi, Chun-yang ; Yan, Sen ; Xu, Hao ; Zeng, Chun-Yuan ; Chen, Jia-Hui ; Hu, Jun-qi ; Li, Yin-long ; Gao, Ya-Biao ; Wei, Jun-jie ; Wei, Jun-Jie ; Wang, Tao ; Liang, Steven H ; Dong, Chen-Chen ; Wei, Hui-yi ; Ma, Jie ; Gao, Ya-biao ; Jiang, Yuan-Fang ; Liao, Kai ; Wei, Hui-Yi ; Chen, Jia-hui ; Dong, Chen-chen ; Hu, Jun-Qi ; Bi, Chun-Yang

Positron emission tomography (PET) targeting translocator protein 18 kDa (TSPO) can be used for the noninvasive detection of neuroinflammation. Improved in vivo stability of a TSPO tracer is beneficial for minimizing the potential confounding effects of radiometabolites. Deuteration represents an important strategy for improving the pharmacokinetics and stability of existing drug molecules in the plasma. This study developed a novel tracer via the deuteration of [¹⁸F]LW223 and evaluated its in vivo stability and specific binding in neuroinflammatory rodent models and nonhuman primate (NHP) brains. Compared with LW223, D₂-LW223 exhibited improved binding affinity to TSPO. Compared with [¹⁸F]LW223, [¹⁸F]D₂-LW223 has superior physicochemical properties and favorable brain kinetics, with enhanced metabolic stability and reduced defluorination. Preclinical investigations in rodent models of LPS-induced neuroinflammation and cerebral ischemia revealed specific [¹⁸F]D₂-LW223 binding to TSPO in regions affected by neuroinflammation. Two-tissue compartment model analyses provided excellent model fits and allowed the quantitative mapping of TSPO across the NHP brain. These results indicate that [¹⁸F]D₂-LW223 holds significant promise for the precise quantification of TSPO expression in neuroinflammatory pathologies of the brain.

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Alzheimer Disease	Preclinical	DE	Bayer AG	-

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